基于高迁移率族蛋白B1对老鼠生物碱A抗肝纤维化作用机制的研究
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基于高迁移率族蛋白B1对老鼠生物碱A抗肝纤维化作用机
制的研究
莫思燕;韦明中;邱金慧;朱勋帅;刘林;林军
【期刊名称】《中国药理学通报》
【年(卷),期】2016(032)011
【摘要】Aim To investigate anti-hepatic fibrotic mechanism of Acanthus ilicifolius alkaloid A ( HBOA ) involved in high mobility group box 1
( HMGB1 ) . Methods A hepatic fibrosis model of rat was estab-lished by the olive oil of CCl4 for 12 weeks. Then, at the 8th week,the successful model rats were randomly divided into model control group, colchicine group, HBOA high-dose group and HBOA low-dose group. From the 9th week,the rats in each group were treated with the drugs daily for 4 weeks respectively. The changes of liver histopathology and collagen were ob-served by HE staining and Masson staining, and the serum indicators including aspartate aminotransferase (AST),alanine aminotransferase(ALT) , total biliru-bin ( T-BIL ) , HMGB1 , interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α) were determined. Moreover , the protein of HMGB1 in liver was examined by immunohistochemistry, and the expression of HMGB1 mRNA was measured by real-time fluores-cence quantitative PCR. Results Compared with the model control group,HBOA high-dose and HBOA low-dose groups significantly attenuated the fibrotic degree induced by CCl4 , markedly decreased the levels of ALT, AST, T-BIL,
HMGB1, IL-1β, TNF-α. Moreo-ver, the expression of HMGB1 protein and mRNA in liver was decreased. And furthermore, serum HMGB1 level had significant positive correlation with IL-1β, TNF-α,ALT,AST and T-BIL. Conclusion HBOA has beneficial effects against liver fibrosis in rat which is induced by CCl4 , the mechanisms may be related to the inhibition of inflammatory response to HMGB1 .%目的:基于高迁移率族蛋白B1( HMGB1)探讨老鼠簕生物碱A( HBOA)抗大鼠肝纤维化的作用机制。
方法采用四氯化碳( CCl4)橄榄油溶液灌胃12周,建立大鼠肝纤维化模型。
第8周确定建模成功后,将其随机分为模型对照组、秋水仙碱组、HBOA 高剂量组、HBOA 低剂量组,从第9周起,相应药物干预4周后,取肝组织切片行 HE 染色及Masson染色;测定血清中 ALT、AST、T-BIL、HMGB1、IL-1β、TNF-α的含量;免疫组化法检测肝组织中HMGB1蛋白的表达;实时荧光定量PCR 法测定肝组织中HMGB1 mRNA表达量。
结果与模型对照组相比, HBOA 高、低剂量均明显减轻CCl4所致肝组织病变程度,降低血清中ALT、AST、T-BIL、HMGB1、IL-1β、TNF-α含量,减少肝组织中HMGB1蛋白及mRNA 表达,且血清 HMGB1水平与 IL-1β、TNF-α、ALT、AST、T-BIL呈正相关。
结论 HBOA对CCl4诱导的大鼠肝纤维化有一定的改善,其作用机制可能与降低致炎因子HMGB1有关。
【总页数】6页(P1553-1558)
【作者】莫思燕;韦明中;邱金慧;朱勋帅;刘林;林军
【作者单位】广西医科大学药学院药理学教研室,广西南宁 530021;广西医科大学药学院药理学教研室,广西南宁 530021;广西医科大学药学院药理学教研室,广西南宁 530021;广西医科大学药学院药理学教研室,广西南宁 530021;广西医
科大学药学院药理学教研室,广西南宁 530021;广西医科大学药学院药理学教研室,广西南宁 530021
【正文语种】中文
【中图分类】R-332;R322.47;R392.12;R575.2;R977.6
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